Journal
JOURNAL OF IMMUNOLOGY
Volume 185, Issue 12, Pages 7405-7412Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1002305
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Funding
- NCI NIH HHS [R21 CA131656, R21 CA131656-01A1] Funding Source: Medline
- NIAID NIH HHS [T32 AI007051, F31 AI077305, R01 AI067467-04, R01 AI067467] Funding Source: Medline
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FcR-like (FCRL) 2 is a transmembrane protein with immunomodulatory potential that is preferentially expressed by memory B cells in humans. It has two consensus ITIMs in addition to a putative ITAM sequence in its cytoplasmic domain. We have confirmed the cellular distribution of FCRL2 and analyzed its functional potential to show that coligation with the BCR leads to tyrosine phosphorylation of its ITIM motifs and subsequent Src homology region 2 domain-containing phosphatase-1 recruitment to facilitate inhibition of BCR signaling. Mutational analysis indicates that the tyrosine residues in both inhibitory motifs of FCRL2 are required for complete inhibition of BCR signaling, whereas tyrosines in the putative activation motif are dispensable for signal modulation. These findings suggest a negative immunomodulatory function for FCRL2 in the regulation of memory B cells. The Journal of Immunology, 2010, 185: 7405-7412.
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